A clique is a set of nodes in which each node of graph is connected to every
other node. Studies of cliques can help to understand ligand-induced population
shift in protein [37].
There are several software packages, Web servers, and plug-ins available for
construction and analyzing of RINs, such as Xpyder (http://xpyder.sourceforge.net/)
[38], Network View [39], RING (http://protein.bio.unipd.it/ring/) [21, 40],
RINalyzer (http://www.rinalyzer.de) [41], structureViz (http://www.cgl.ucsf.edu/
cytoscape/structureViz/) [42].
Web server RING constructs physicochemically RINs from PDB files for subsequent visualization in the Cytoscape (software platform for the analysis and
visualization of biological networks) (http://www.cytoscape.org) or Pymol (https://
pymol.org/). Interactions (edges) are disulfide bonds, salt bridges, hydrogen bonds,
aromatic interactions, and van der Waals contacts. Several features can be added to
nodes and edges, such as secondary structure, solvent accessibility, energy score,
sequence conservation. Subnetwork can be also constructed.
RINalyzer and structureViz are plug-ins for Cytoscape [43] that link Cytoscape
with the molecular viewer UCSF Chimera (http://www.cgl.ucsf.edu/chimera/) [44].
They allow interactive structure analysis of RINs together with the corresponding
3D protein structure.
NetworkView plug-in for VMD (https://www.ks.uiuc.edu/Research/vmd/)
allows to study allostery and signaling through network models. This plug-in can
display the dynamical network representations.
3 RINs Application
3.1 Ligand Binding Sites
Identification of the ligand binding sites of proteins and functionally important
residues is a crucial first step in drug design. However, it is a difficult task in the
case of the absence of homologous proteins.
Several topological parameters of RINs may be used for the prediction of ligand
binding sites. Several investigations showed that closeness and betweenness values
of residues are correlated with ligand binding site residues [14, 34, 45–48]. The
accuracy of prediction such residues may be improved by combining with such
parameters as their solvent accessibility. So, Amitai et al. [14] could predict active
site residues in 70% of the analyzed 178 enzymes proteins, using closeness centrality and solvent accessibility parameters. The similar result was obtained in [49].
The closeness centrality was used as parameter in machine learning methods for
prediction of functionally important residues [50] or in score for docking [25].
However, for non-enzyme proteins correlation between closeness centrality and
binding sites has not observed [34, 51]. In addition, global closeness centrality gave
unsatisfactory result for non-globular and oligomer proteins. For such proteins,
Analysis of Protein Structures Using Residue Interaction …
59
other node. Studies of cliques can help to understand ligand-induced population
shift in protein [37].
There are several software packages, Web servers, and plug-ins available for
construction and analyzing of RINs, such as Xpyder (http://xpyder.sourceforge.net/)
[38], Network View [39], RING (http://protein.bio.unipd.it/ring/) [21, 40],
RINalyzer (http://www.rinalyzer.de) [41], structureViz (http://www.cgl.ucsf.edu/
cytoscape/structureViz/) [42].
Web server RING constructs physicochemically RINs from PDB files for subsequent visualization in the Cytoscape (software platform for the analysis and
visualization of biological networks) (http://www.cytoscape.org) or Pymol (https://
pymol.org/). Interactions (edges) are disulfide bonds, salt bridges, hydrogen bonds,
aromatic interactions, and van der Waals contacts. Several features can be added to
nodes and edges, such as secondary structure, solvent accessibility, energy score,
sequence conservation. Subnetwork can be also constructed.
RINalyzer and structureViz are plug-ins for Cytoscape [43] that link Cytoscape
with the molecular viewer UCSF Chimera (http://www.cgl.ucsf.edu/chimera/) [44].
They allow interactive structure analysis of RINs together with the corresponding
3D protein structure.
NetworkView plug-in for VMD (https://www.ks.uiuc.edu/Research/vmd/)
allows to study allostery and signaling through network models. This plug-in can
display the dynamical network representations.
3 RINs Application
3.1 Ligand Binding Sites
Identification of the ligand binding sites of proteins and functionally important
residues is a crucial first step in drug design. However, it is a difficult task in the
case of the absence of homologous proteins.
Several topological parameters of RINs may be used for the prediction of ligand
binding sites. Several investigations showed that closeness and betweenness values
of residues are correlated with ligand binding site residues [14, 34, 45–48]. The
accuracy of prediction such residues may be improved by combining with such
parameters as their solvent accessibility. So, Amitai et al. [14] could predict active
site residues in 70% of the analyzed 178 enzymes proteins, using closeness centrality and solvent accessibility parameters. The similar result was obtained in [49].
The closeness centrality was used as parameter in machine learning methods for
prediction of functionally important residues [50] or in score for docking [25].
However, for non-enzyme proteins correlation between closeness centrality and
binding sites has not observed [34, 51]. In addition, global closeness centrality gave
unsatisfactory result for non-globular and oligomer proteins. For such proteins,
Analysis of Protein Structures Using Residue Interaction …
59